EFFECT OF AMIODARONE ON CLINICAL STATUS AND LEFT-VENTRICULAR FUNCTIONIN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Background Although trials of amiodarone therapy in patients with cong estive heart failure have produced discordant results with regard to e ffects on survival, most studies have reported a significant rise in l eft ventricular ejection fraction during long-term therapy. In the pre sent study, we determined whether this increase in ejection fraction i s associated with an improvement in the symptoms and/or physical findi ngs of heart failure or a reduction in the number of hospitalizations for heart failure. Methods and Results In the Department of Veterans A ffairs cooperative study of amiodarone in congestive heart failure, 67 4 patients with New York Heart Association class II through IV symptom s and ejection fractions of less than or equal to 40% were treated wit h amiodarone or placebo for a median of 45 months in a randomized, dou ble-blind, placebo-controlled protocol. Clinical assessments and radio nuclide ejection fraction were performed at baseline and after 6, 12, and 24 months. Compared with the placebo group, ejection fraction incr eased more in the amiodarone group at each time point (8.1 +/- 10.2% [ mean +/- SD] versus 2.6 +/- 7.9% at 6 months, 8.0 +/- 10.9% versus 2.7 +/- 8.0% at 12 months, and 8.8 +/- 10.1% versus 1.9 +/- 9.4% after 24 months, all P<.001). However, this difference was not associated with greater clinical improvement, lesser diuretic requirements, or fewer hospitalizations for heart failure (11.1% for amiodarone and 13.6% for placebo group; overall relative risk in the amiodarone group, 0.81 [9 5% CI, 0.56 to 1.10] P=.18). Of note is the trend toward a reduction i n the combined end point of hospitalizations and cardiac deaths (relat ive risk, 0.82 [CI, 0.65 to 1.03], P=.08), which was significant in pa tients with nonischemic etiology (relative risk, 0.56 [CI, 0.36 to 0.8 7], P=.01) and absent in the ischemic group (relative risk, 0.95). Con clusions Although amiodarone therapy resulted in a substantial increas e in left ventricular ejection fraction in patients with congestive he art failure, this was not associated with clinical benefit in the popu lation as a whole. The substantial reduction in the combined end point of cardiac death plus hospitalizations for heart failure in the nonis chemic group suggests possible benefit in these patients.